A flat mink cell line which contains the defective Maloney murine sarcoma viral genome (S positive L negative mink) becomes transformed upon superinfection with a helper virus. In the absence of helper virus, dexamethasone (10 to the minus 8th power M) treatment of S positive L negative mink induces a morphologocially similar transformation. Removal of dexamethasone is followed by loss of transformation. The ability of other steroid hormones to induce this change parallels their glucocorticoid activity. By immunofluorescence, the transformed cells contain markedly increased levels of viral antigen. Transformation is accompanied by an increase in both Maloney sarcoma viral RNA and murine p30; these parameters fall to pretreatment levels following removal of glucocorticoid. No intact virus has been demonstrated. The parental mink cell line from which the S plus L minus mink was derived does not show these dexamethasone induced changes. These observations represent the first glucocorticoid dependent transformation system and the first documented increase in a C-type viral RNA by glucocorticoids. The results suggest that the glucocorticoid induced transformation is mediated through induction of the sarcoma viral genome.